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microRNA‐124 regulates Notch and NeuroD1 to mediate transition states of neuronal development

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MicroRNAs regulate gene expression by destabilizing target mRNA and/or inhibiting translation in animal cells. The ability to mechanistically dissect miR‐124′s function during specification, differentiation, and maturation of neurons during development… Click to show full abstract

MicroRNAs regulate gene expression by destabilizing target mRNA and/or inhibiting translation in animal cells. The ability to mechanistically dissect miR‐124′s function during specification, differentiation, and maturation of neurons during development within a single system has not been accomplished. Using the sea urchin embryo, we take advantage of the manipulability of the embryo and its well‐documented gene regulatory networks (GRNs). We incorporated NeuroD1 as part of the sea urchin neuronal GRN and determined that miR‐124 inhibition resulted in aberrant gut contractions, swimming velocity, and neuronal development. Inhibition of miR‐124 resulted in an increased number of cells expressing transcription factors (TFs) associated with progenitor neurons and a concurrent decrease of mature and functional neurons. Results revealed that in the early blastula/gastrula stages, miR‐124 regulates undefined factors during neuronal specification and differentiation. In the late gastrula/larval stages, miR‐124 regulates Notch and NeuroD1 during the transition between neuronal differentiation and maturation. Overall, we have improved the neuronal GRN and identified miR‐124 to play a prolific role in regulating various transitions of neuronal development.

Keywords: regulates notch; mir 124; development; 124 regulates; neuronal development; notch neurod1

Journal Title: Developmental Neurobiology
Year Published: 2022

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